US10786522B2 - Compositions that include anthocyanidins and methods of use - Google Patents

Compositions that include anthocyanidins and methods of use Download PDF

Info

Publication number
US10786522B2
US10786522B2 US13/076,117 US201113076117A US10786522B2 US 10786522 B2 US10786522 B2 US 10786522B2 US 201113076117 A US201113076117 A US 201113076117A US 10786522 B2 US10786522 B2 US 10786522B2
Authority
US
United States
Prior art keywords
delphinidin
compositions
anthocyanidins
composition
rich
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active, expires
Application number
US13/076,117
Other languages
English (en)
Other versions
US20110268825A1 (en
Inventor
Rafael Burgos
Juan Hancke
Evelyn Jara
Maria Hidalgo
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pharmaceutical Patent Attorneys LLC
Original Assignee
Maqui New Life S A
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US13/076,117 priority Critical patent/US10786522B2/en
Application filed by Maqui New Life S A filed Critical Maqui New Life S A
Assigned to CONSORCIO DE TECNOLOGIA E INNOVACION PARA LA SALUD S.A. reassignment CONSORCIO DE TECNOLOGIA E INNOVACION PARA LA SALUD S.A. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BURGOS, RAFAEL, HANCKE, JUAN, HIDALGO, MARIA, JARA, EVELYN
Assigned to MAQUI NEW LIFE SA (MNL) reassignment MAQUI NEW LIFE SA (MNL) ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CONSORCIO DE TECNOLOGIA E INNOVACION PARA LA SALUD S.A.
Publication of US20110268825A1 publication Critical patent/US20110268825A1/en
Priority to US14/587,070 priority patent/US20150164932A1/en
Priority to US16/256,384 priority patent/US20190151342A1/en
Assigned to Pharmaceutical Patent Attorneys, LLC reassignment Pharmaceutical Patent Attorneys, LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MAQUI NEW LIFE S.A.
Publication of US10786522B2 publication Critical patent/US10786522B2/en
Application granted granted Critical
Assigned to Pharmaceutical Patent Attorneys, LLC reassignment Pharmaceutical Patent Attorneys, LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MAQUI NEW LIFE S.A.
Active legal-status Critical Current
Adjusted expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A23V2250/2104—Anthocyanins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A23V2250/2106—Bilberries, blueberries

Definitions

  • compositions that generally include certain amounts and types of anthocyanidins and/or their glycoside counterparts. These compositions can be made and used alone or made and used in combination with other compositions, for example, those containing an andrographolide.
  • the compositions can be formulated as pharmaceutical preparations or incorporated into foods such as drinks and cereal bars. Their administration or consumption helps maintain immune function, stimulates the immune system, reduces inflammation, and protects against other unwanted conditions (e.g., metabolic syndrome).
  • Anthocyanidins and anthocyanins are a large family of naturally occurring pigments. The color of most fruits, flowers and berries is determined by their content of anthocyanidins and anthocyanins.
  • anthocyanidins have been suggested that anthocyanidins and anthocyanidin derivates can exhibit antiviral effects in infected cells and antineoplastic effects in neoplastic cells (see PCT/NO97/00100 (WO 97/41137)).
  • Anthocyanin-rich extracts are also disclosed for the treatment of a disordered metabolism syndrome (see U.S. Application Publication No. 2009/0176718).
  • compositions that include an anthocyanin or anthocyanidin preparation that is rich in delphinidin(s). While there has been significant interest in anthocyanins and in the antioxidant properties of berry extracts, this is, to our knowledge, the first description of compositions that include not only a certain amount of anthocyanins and/or anthocyanidins, but also a certain amount and/or a certain type of a delphinidin. The various compositions and methods of the invention have other distinguishing characteristics as well.
  • the compositions of the present invention include one or more anthocyanidins and/or aglycolic anthocyanins that have been enriched for one or more delphinidins.
  • the amount or type of the anthocyanidins or anthocyanins or the amount or type of the delphinidins (or both) may differ from (e.g., exceed) that found in a naturally occurring composition such as a berry or other plant part or product.
  • the delphinidin-containing (e.g., delphinidin-rich) compositions can include additional specific compounds such as an adrographolide (e.g., from a plant of the genus Andrographis ).
  • the delphinidin-containing (e.g., delphinidin-rich) compositions can include specific compounds such as one or more of: myrtillin, cyanidin, quercetin, a caffeoylquinic derivative, a proanthocyanidin and/or proanthocyanin (e.g., as found in the herba (e.g., leaves) of a plant of the genus Vaccinium ).
  • compositions that consist of or that include a plurality of anthocyanins and/or anthocyanidins in which (a) at least or about 35% of the composition, by weight, is an anthocyanin or anthocyanidin and (b) at least or about 15% of the anthocyanins and/or anthocyanidins, by weight, are sugar-free or sugar-containing delphinidins.
  • compositions and any of the compositions of the invention can be non-toxic, and all are non-naturally occurring (i.e., none are identical to a product of nature).
  • compositions can include sugar-containing delphinidin, such as a delphinidin glucoside (e.g., delphinidin-3-O-sambubioside-5-O-glucoside).
  • a delphinidin glucoside e.g., delphinidin-3-O-sambubioside-5-O-glucoside
  • the amount of the delphinidin can vary according to the parameters set out herein. For example, at least or about 15% of the anthocyanins and/or anthocyanidins, by weight (e.g., at least or about 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%), can be a delphinidin such as delphinidin-3-O-sambubioside-5-O-glucoside.
  • At least or about 5% of the composition as a whole, by weight can be a delphinidin such as delphinidin-3-O-sambubioside-5-O-glucoside.
  • compositions of the invention one or more, including all, of the anthocyanins or anthocyanidins can conform to the following formula:
  • each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are, independently, —H, —OH, or OCH 3 (see Table 1, below).
  • compositions of the invention can be formulated for oral consumption (e.g., as an ingredient of a food product) or oral administration (e.g., as a tablet, pill, capsule, caplet, and the like), or they can be formulated for administration by a parenteral route.
  • compositions of the invention can also include an andrographolide and can be enriched for andrographolides (e.g., the andrographolide can constitute, by weight, at least or about 10% (e.g., at least or about 10%, 15%, 20%, 25%, 30% or more) of the composition.
  • the andrographolide can be an andrographolide, a deoxyandrographolide, a neoandrographolide, or a mixture thereof, and it may be contained within an extract of a plant of the genus Andrographis (e.g., Andrographus paniculata ).
  • the amount of the andrographolide may also be expressed relative the amount of the anthocyanins and/or anthocyanidins, and the ratio of anthocyanin and/or anthocyanidin to andrographolide can be about 1.0:0.1 to about 1.0:10 (w:w) (e.g. 1.0:0.5 to about 1.0:2.5 (w:w).
  • compositions that include can include at least or about 15% (e.g., at least or about 15%, 20%, 25%, 30%, or more) myrtillin, quercetin, and/or cyanidin.
  • composition of the invention includes a proanthocyanin or proanthocyanidin
  • it can be one extracted from a plant of the genus Vaccinium (e.g., Vaccinium augustifolium and/or Vaccinium myrtillus ).
  • composition of the invention includes a caffeoylquinate derivative, it can be chlorogenate or chlorogenic acid.
  • the amounts of proanthocyanins and/or proanthocyanidins can be expressed relative to the anthocyanins and/or anthocyanidins.
  • the ratio of the plurality of anthocyanins and/or anthocyanidins to the proanthocyanin and/or proanthocyanidin can be is about 1.0:0.1 to about 1.0:10 (w:w) (e.g., about 1.0:0.5 to 1.0:2.5 (w:w)).
  • the ratio of the plurality of anthocyanins and/or anthocyanidins to the caffeoylquinate derivative can also be about 1.0:0.1 to about 1.0:10 (w:w) (e.g., about 1.0:0.5 to 1.0:2.5 (w:w)).
  • the pharmaceutical compositions of the invention can include (a) a first composition comprising a carrier and (b) about 100 mg to 400 mg of a second composition comprising one or more anthocyanins and/or anthocyanidins, wherein the anthocyanins and/or anthocyanidins constitute at least 35% of the first composition and at least 15% of the anthocyanins and/or anthocyanidins are sugar-free or sugar-containing delphinidins.
  • the first composition can include microcrystalline cellulose, lactose, silicon dioxide, glyceryl monostearate, soya lecithin, or Oenothera biennis oil.
  • the pharmaceutical compositions described above can include about 35%-45% of a second composition containing an anthocyaninin or anthocyanidin and about 15-50% of the anthocyaninins or anthocyanidins can be sugar-free or sugar-containing delphinidins.
  • the pharmaceutical compositions can also include a third composition comprising an andrographolide (e.g., about 30-40% of the third composition is an andrographolide).
  • the ratio of the second composition comprising the anthocyaninins and/or anthocyanidins to the third composition comprising the andrographolide can be about 1.0:0.5 to 1.0:3.0 (w:w).
  • the compositions can be formulated as capsules (e.g., as a soft cellulose capsule or hard gelatine capsule).
  • the invention features pharmaceutical compositions comprising: 100-400 mg of a first composition comprising anthocyanidins, wherein about 41% of the first composition is an anthocyanin or anthocyanidin and about 35% of the anthocyanins or anthocyanidins are sugar-free or sugar-containing delphinidins; 300 mg of a second composition comprising an andrographolide, wherein about 35% of the second composition is the andrographolide; and a third composition comprising a carrier, wherein the third composition, optionally, includes one or more of glyceryl monostearate, soya lecithin, Oenothera biennis oil, microcrystalline cellulose, lactose, silicon dioxide, povidone, and sodium carboxymethylcellulose.
  • the third composition can include 30 mg of glyceryl monostearate, 20 mg of soya lecithin, and 700 mg Oenothera biennis oil; 400 mg of microcrystalline cellulose, 95 mg of lactose, and 10 mg of silicon dioxide; or 400 mg microcrystalline cellulose, 15 mg povidone, and 10 mg sodium carboxymethylcellulose.
  • the pharmaceutical compositions can include (a) a first composition comprising a carrier, (b) about 100 mg to 400 mg of a second composition comprising one or more anthocyanins and/or anthocyanidins, wherein the anthocyanins and/or anthocyanidins constitute at least 35% of the first composition and at least 15% of the anthocyanins and/or anthocyanidins are sugar-free or sugar-containing delphinidins, and (c) a third composition comprising caffeeoylquinic acid.
  • the invention features methods of maintaining immune function in a subject by, inter alia, administering to the subject a composition as described herein, and the subject may have no overt condition known to compromise the immune system.
  • the composition can be administered in an amount and for a time sufficient to maintain immune function.
  • the subject can be a human, although the invention is not so limited, and any of the present methods can be expressed in terms of a “use” of the compositions.
  • the method just described can be expressed as use of a compositions as described herein for the preparation of a medicament (e.g., the preparation of a medicament for use in maintaining immune function).
  • the methods can further include a step of prescribing, for the subject, dietary standards and/or an exercise program.
  • a subject to be treated can be an animal kept as a domestic pet or as livestock, and where the subject is an animal kept as livestock, the administration of the composition may reduce or obviate the need for prophylactic antibiotic treatment.
  • Livestock includes, inter alia, a cow, sheep, pig, chicken, turkey, or duck.
  • the invention features methods of treating a patient who has a condition in which the immune system is undesirably suppressed by administering a composition as described herein in an amount and for a time sufficient to stimulate the patient's immune system.
  • the patient can be a human and the condition can be cancer or an acquired immunodeficiency syndrome.
  • the invention features methods of treating inflammation in a subject by administering to the subject a composition as described herein in an amount and for a time sufficient to reduce or improve a sign or symptom of inflammation in the subject.
  • the subject can be a human and the inflammation can be caused by a burn or other traumatic injury, a chemical irritant or toxin, an infection (e.g., a bacterial or viral infection), or an autoimmune disease.
  • the invention features methods of treating metabolic syndrome in a patient by administering to the subject a composition as described herein in an amount and for a time sufficient to reduce or improve a sign or symptom of metabolic syndrome in the patient.
  • the patient can be a human, and the metabolic syndrome can be associated with diabetes or Syndrome X, or CHAOS.
  • FIG. 1 shows the average spectrofluorescence results for 4 measurements of calcium fluxes in Jurkat T cells treated with compositions of delphinidin.
  • FIG. 2A shows the spectrofluorescence results for the average of 4 measurements of calcium fluxes in Jurkat T cells treated with the composition comprising delphinidin 50 ⁇ M.
  • FIG. 2B shows the spectrofluorescence results for the average of 4 measurements of calcium fluxes in Jurkat T cells treated with the composition comprising delphinidin 50 ⁇ M and BTP-2 10 ⁇ M.
  • FIG. 3 shows the spectrofluorescence results for Jurkat T cells pretreated with U73122 100 ⁇ M or 50 ⁇ M, and treated with delphinidin 50 ⁇ M.
  • FIG. 4A shows COX-2 levels in an immunoblot of CaCo-2 cells treated with the composition comprising a final concentration in the samples of 1.75 ⁇ g/ml of anthocyanidins rich in delphinidins after 0, 24, 48, and 72 hrs.
  • FIG. 4B shows RNAm COX-2 expression levels in a real time PCR of CaCo-2 cells treated with the composition comprising a final concentration in the samples of 1.75 ⁇ g/ml of anthocyanidins rich in delphinidins after 24 hrs.
  • FIG. 4C shows COX-2 expression levels in an immunoblot of human neutrophils preincubated during 30 minutes with a composition according to the present invention considering a final concentration in the samples of 1.75 ⁇ M of anthocyanidins rich in delphinidins, or with a composition according to the present invention considering a final concentration in the samples of 1.75 ⁇ M of anthocyanidins rich in delphinidins and 50 ⁇ M andrographolides and treated with fMLP during 3 hours.
  • FIG. 5 shows PPar- ⁇ activation compared to the control in HL-60 cells transfected with a reporter vector PPar- ⁇ -Luc, and treated with a composition according to the invention comprising final concentrations in the samples of 0.175 ⁇ g/ml, 1.75 ⁇ g/ml, 17.5 ⁇ g/ml anthocyanidins rich in delphinidins, or treated with PMA, PGj2 or TNF ⁇ for 12 hrs.
  • FIG. 6 shows the results for glycemia increase levels in the three groups of treatment of rats: control group, treated with water; group treated with a composition according to the invention considering a dose of 7 mg/kg of anthocyanidins rich in delphinidins; and group treated with a composition according to the invention considering a dose of 70 mg/kg of anthocyanidins rich in delphinidins; and the effecrof the compositions according to the invention for reducing this increased levels.
  • compositions that comprise anthocyanidins, more preferably delphinidins, alone or combined with other compositions that comprise compounds selected among andrographolides, caffeoyl quinic derivatives and proanthocyanidins.
  • the compositions can be formulated in various ways.
  • formulations within the invention include the compositions per se, compact oral formulations (e.g., capsules or “gel tabs” including the extracts and a carrier), and food products (e.g., juices or cereal bars).
  • the invention features methods of using these compositions to stimulate the immune system of a subject, to maintain immune function in a subject who does not have an overt condition (i.e., to promote or maintain immune function in a seemingly healthy person (e.g., a person who has not been diagnosed with an infection or immune disease)), treat a subject who has a recognizable condition (e.g., an infection), treat an inflammation condition in a subject or to improve a sign or symptom of metabolic syndrome.
  • an overt condition i.e., to promote or maintain immune function in a seemingly healthy person (e.g., a person who has not been diagnosed with an infection or immune disease)
  • a subject who has a recognizable condition e.g., an infection
  • any of the present methods can include a step of identifying a patient in need of treatment. For example, a subject can be examined and/or subjected to clinical tests in order to determine whether they have, for example, a metabolic disorder or inflammation.
  • metabolic disorders such as Syndrom X, insulin resistance syndrome, Reaven's sydrome, and the syndrome referred to as CHAOS. Diabetes can also be treated.
  • the invention features compositions that comprise anthocyanidin combinations rich in delphinidins.
  • the compositions include one or more compounds found within a plant extract (i.e., where the compositions are based on the extracts but are not extracts per se), the compositions can include some or all of the anthocyanidins naturally found within the extract.
  • the composition e.g., a nutriceutical or food product
  • the anthocyanidin can conform to the following formula:
  • each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are, independently, —H, —OH, or —OCH 3 , and wherein at least 15% of the anthocyanidins (e.g., at least or about 15%, 20%, 25%, 30%, 40%, 45%, 50%, or more of the anthocyanidins) are delphinidins.
  • the anthocyanidin combinations rich in delphinidins can include both delphinidins and cyanidins
  • compositions of the present invention are not limited to those in which a particular amount of the anthocyanidin is present, at least (or about) 35% of the compositions that comprise anthocyanidin combinations rich in delphinidins (e.g., at least or about 35, 40, 41, 42, 43, 44, 45 or 50% of the compositions that comprise anthocyanidin combinations rich in delphinidins) can be an anthocyanidin of Formula I.
  • Anthocyanins are water-soluble vacuolar flavonoid pigments that may appear red, purple or blue according to pH. Anthocyanins occur in tissues of higher plants and provide color in leaves, stems, roots, flowers and fruits. In photosynthetic tissues (such as leaves and some stems), anthocyanins protect cells from high-light damage by absorbing blue-green and UV light, thereby protecting the tissues from photoinhibition.
  • the anthocyanins are mostly 3-glucosides of the anthocyanidins.
  • the anthocyanins are subdivided into the sugar-free anthocyanidin aglycones and the anthocyanin glycosides.
  • the compositions that comprise anthocyanidin combinations rich in delphinidins can include a mixture of anthocyanidins.
  • the combinations of anthocyanidins rich in delphinidins can also comprise cyanidins.
  • the present compositions can include combinations of anthocyanidins that are extracted from a plant, optionally including the fruit or other edible plant product, of the genus Aristotelia, Aronia, Enterpe, Glycine, Prunus, Ribes, Rubus, Sambucus, Vaccinium , or Zea .
  • the extract can be made from the plant Aristotelia chilensis .
  • the fruit or other edible plant product can be an acai berry, a bilberry, a black currant, a black soybean, a blackberry, blue com, a blueberry, a cherry, a chokeberry, a cranberry, an elderberry, a gooseberry, a maqui berry, purple com, a raspberry, or a red currant.
  • Plants of the Vaccinium species such as blueberry, cranberry and bilberry, Rubus berries including black raspberry, red raspberry and blackberry, blackcurrant, cherry, eggplant peel.
  • black rice, Concord grape and muscadine grape, red wine, red cabbage and violet petals are rich in anthocyanins and can be used as a source of the present extracts.
  • anthocyanins are less abundant in banana, asparagus, pea, fennel, pear and potato, the fruits of these plants may also be used in making the present compositions.
  • High amounts of anthocyanins are found in the seed coat of black soybean ( Glycine max L. Men.) (2000 mg/100 g) and in skins and pulp of black chokeberry ( Aronia melanocarpa L.) (1480 mg/100 g), which are also useful in making the present compositions.
  • Aristotelia chilensis the main components are derivatives of cyanidin and delphinidin in the form of diglycosides, which are commonly present in the fruits at a concentration between about 0.9 and 1.5%.
  • the combinations of anthocyanidins can be prepared from any plant material that includes anthocyanins, such as berries from one or more plants in the genus Aristotelia (e.g., Aristotelia chilensis ) or Vaccinium (e.g., Vaccinium augustifolium or corimbosum ).
  • Aristotelia e.g., Aristotelia chilensis
  • Vaccinium e.g., Vaccinium augustifolium or corimbosum
  • compositions can further include a carrier or excipient (e.g., an oil, including a plant or animal oil (e.g., fish oil)) and can be formulated for oral administration.
  • a carrier or excipient e.g., an oil, including a plant or animal oil (e.g., fish oil)
  • oils rich in polyunsaturated ⁇ -3 acids such as Oenothera biennis or Linum usatissimum oils or fish oil.
  • Any of the present compositions may also contain adjuvants including preservative agents, wetting agents, emulsifying agents, and dispersing agents.
  • the action of microorganisms may be inhibited by the inclusion of an antibacterial, antifungal, or antiviral agent (e.g., parabens, chlorobutanol, phenol, sorbic acid, and the like).
  • Suitable buffering agents include: acetic acid and a salt (1-2% w/v); citric acid and a salt (1-3% w/v); boric acid and a salt (0.5-2.5% w/v); and phosphoric acid and a salt (0.8-2% w/v).
  • Suitable preservatives include benzalkonium chloride (0.003-0.03% w/v); chlorobutanol (0.3-0.9% w/v); parabens (0.01-0.25% w/v) and thimerosal (0.004-0.02% w/v).
  • compositions for oral administration, can be formulated as a tablet, dragee, or capsule (e.g., a hard or soft gelatin capsule or a cellulose-based capsule).
  • a tablet, dragee, or capsule e.g., a hard or soft gelatin capsule or a cellulose-based capsule.
  • any of the present compositions can be formulated as, or incorporated into, a food product.
  • the form of the food product can vary greatly and includes any drink or beverage (i.e., a solution ingested in liquid form), cereal or cereal-type bar or “energy” bar.
  • the present compositions can include a composition as described herein, a beverage component and a diluent.
  • the beverage component can include components to enhance the efficacy of the beverage in providing benefits such as fighting infection, providing a desirable nutritional profile, and for providing enhanced organoleptic properties.
  • the beverage component can be tea, a carbonated drink, or a nutritional drink.
  • the beverage component can further include one or more bracers or flavanols, sugar or non-caloric sweeteners, vitamins, flavouring agents, coloring agents, preservatives, acidulants, or diluents (e.g., water).
  • the extracts or active compounds therein may be dispersed, solubilized, or otherwise mixed into the beverage formulation of the instant invention.
  • compositions comprising anthocyanidin combinations rich in delphinidin can be used to treat a subject who has a condition in which the immune system is undesirably suppressed.
  • a composition comprising an anthocyanidin combination rich in delphinidins can act as an immunostimulant in a subject whose immune system is depressed.
  • Compositions that are generated from purified or synthesized compounds e.g., mixtures of anthocyanidins
  • the compositions can be administered to a subject (e.g., a human) in an amount and for a time sufficient to promote immunostimulation in the subject.
  • the immune suppression can occur, for example, in subjects who have cancer or acquired immunodeficiency syndrome.
  • compositions rich in delphinidin are useful in maintaining immune function in a subject (e.g., a human), including subjects who do not have any overt condition that is compromising the immune system.
  • These methods encompass administering to the subject a composition that comprises a combination of anthocyanins and is rich in delphinidin.
  • the compositions are administered in an amount and for a time sufficient to maintain immune function in the subject.
  • these compositions are useful in maintaining immune function and therefore promoting or supporting a healthy condition, they can be administered in conjunction with a diet program and for an exercise-program.
  • These and any other of the present compositions can also be taken with meals. Immunity decreases with age, and natural immune responses are adversely affected both as a person ages and in association with numerous conditions.
  • compositions comprising anthocyanidin combinations rich in delphinidins can be used in any circumstance where one wishes to counteract the natural decay of immunity.
  • they can be administered to a generally healthy person.
  • the person may be of a certain age (e.g., a man over fifty years old or a peri- or post-menopausal woman).
  • compositions comprising anthocyanidin combinations rich in delphinidins can also be used to counteract the decrease in immunity that occurs as a side effect of immunosuppressant treatment or in association with cancer and infections (e.g., bacterial, fungal, or viral infections).
  • infections e.g., bacterial, fungal, or viral infections.
  • compositions comprising anthocyanidin combinations rich in delphinidins can be administered to animals (e.g., animals kept as domestic pets, in zoos, or as livestock).
  • animals e.g., animals kept as domestic pets, in zoos, or as livestock.
  • livestock e.g., a cow, sheep, pig, goat, chicken, turkey, duck, or other bird
  • administration of the composition can obviate the need for prophylactic antibiotic treatment.
  • compositions comprising anthocyanidin combinations rich in delphinidins can also be used to treat inflammation in a subject.
  • a composition comprising an anthocyanidin combination rich in delphinidins can be used to treat inflammation.
  • Compositions that are generated from purified or synthesized compounds e.g., mixtures of anthocyanidins
  • the compositions can be administered to a subject (e.g., a human) in an amount and for a time sufficient to inhibit inflammation in the subject.
  • effective dosages can vary based on a number of parameters and particular dosages can be determined by methodologies known in the art. Generally, we expect therapeutically effective amounts of the present compositions or active ingredients therein to vary from about 0.001 mg/kg body weight to about 10 g/kg body weight (e.g., about 0.005, 0.01, 0.05, 0.1, 1.0, 10.0, 100, 250, or 500 mg/kg body weight). According to some such embodiments, the therapeutically effective amount of a composition comprising an anthocyanidin combination rich in delphinidins is at least or about 1 g/kg per body weight (e.g., at least or about 2.5, 5.0, 7.5, or 10.0 g/kg body weight). These dosages are pertinent regardless of the precise content or intended use.
  • the inflammation can be caused by a variety of conditions or an external injury.
  • the inflammation can be caused by a burn or other traumatic injury, a chemical irritant or toxin, an infection (e.g., a bacterial or viral infection), or an autoimmune disease.
  • compositions that comprise a combination of anthocyanidins rich in delphinidins can be administered to a subject for the treatment of metabolic syndrome.
  • the composition can be administered in an amount and for a time sufficient to improve a sign or symptom of the metabolic syndrome.
  • the method can include a step of identifying a subject who would be expected to benefit from the administration of a composition.
  • the present method can include a step of performing diagnostic tests and/or patient examinations and/or interviews to determine whether a patient has, or is likely to have, metabolic syndrome and would, therefore, be a candidate for treatment with the compositions just described.
  • Metabolic syndrome is associated with obesity and diabetes.
  • compositions that comprise anthocyanidin combinations rich in delphinidin can be used to treat obesity and/or diabetes (e.g., type II diabetes) whether those conditions occur within the context of metabolic syndrome or independent of metabolic syndrome.
  • the compositions that comprise anthocyanidin combinations rich in delphinidin can also be used to help regulate cholesterol levels, including the levels of LDL and triglycerides.
  • the present compositions can be used to treat these conditions in the context of metabolic syndrome or independent of that syndrome.
  • compositions can comprise (a) anthocyanidin combinations rich in delphinidins, and (b) compositions that comprise andrographolides.
  • Delphinidin-rich compositions can be made from purified or synthesized compounds. At least 35% (e.g., at least or about 35%, 40%, 45% or 50%) of the anthocyanidin combinations rich in delphinidins can be an anthocyanidin of the following formula:
  • each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are, independently, —H, —OH, or —OCH 3 , and wherein at least 15% of the anthocyanidins (e.g., at least or about 15%, 20%, 25%, 30%, 40%, 45%, 50%, or more of the anthocyanidins) are delphinidin.
  • the anthocyanidin combinations rich in delphinidins can include both delphinidins and cyanidins, and the compounds can be extracted from a plant, optionally including the fruit or other edible plant product, of the genus Aristotelia (e.g., Aristotelia chilensis ), Aronia, Enterpe, Glycine, Prunus, Ribes, Rubus, Sambucus, Vaccinium , or Zea.
  • Aristotelia e.g., Aristotelia chilensis
  • Aronia Enterpe
  • Glycine Prunus
  • Ribes Rubus
  • Sambucus Vaccinium
  • Zea Zea
  • the fruit or other edible plant product can be an acai berry, a bilberry, a black currant, a black soybean, a blackberry, blue corn, a blueberry, a cherry, a chokeberry, a cranberry, an elderberry, a gooseberry, a maqui berry, purple corn, a raspberry, or a red currant.
  • At least 30% of the compositions that comprise andrographolides can be an andrographolide (e.g., an andrographolide, a deoxyandrographolide, a neoandrographolide, or a mixture thereof).
  • the compositions that comprise andrographolides can be prepared from the herba (e.g., the leaves) of a plant of the genus Andrographis (e.g., Andrographus paniculata ).
  • the ratio of the anthocyanidins combinations rich in delphinidins to the combinations that comprise andrographolides can be about 1.0:0.5 (w:w) to about 1.0:10.0 (w:w) (e.g., about 1.0:0.1, 1.0:0.5, 1.0:1.0, 1.0:1.5, 1.0:2.0, 1.0:2.5, 1.0:3.0, 1.0:3.5, 1.0:4.0, 1.0:4.5, 1.0:5.0, 1.0:5.5, 1.0:6.0, 1.0:6.5, 1.0:7.0, 1.0:7.5, 1.0:8.0, 1.0:8.5, 1.0:9.0, 1.0:9.5, 1.0:10.0, or 1.0:10.5).
  • compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides can be formulated with a carrier or excipient and administered as a nutraceutical or in the context of a food product.
  • compositions comprising anthocyanidin combinations rich in delphinidin combined with compositions that comprise andrographolides can be used to treat a subject who has a condition in which the immune system is undesirably suppressed.
  • a composition comprising an anthocyanidin combination rich in delphinidin combined with a composition that comprise an andrographolides combination can act as an immunostimulant in a subject whose immune system is depressed.
  • Compositions that are generated from purified or synthesized compounds e.g., mixtures of anthocyanidins and andrographolides
  • the compositions can be administered to a subject (e.g., a human) in an amount and for a time sufficient to promote immunostimulation in the subject.
  • the immune suppression can occur, for example, in subjects who have cancer or acquired immunodeficiency syndrome.
  • compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides are useful in maintaining immune function in a subject (e.g., a human), including subjects who do not have any overt condition that is compromising the immune system.
  • These methods encompass administering to the subject a composition that includes compositions comprising a) anthocyanidin combinations rich in delphinidins, and b) compositions that comprise andrographolides
  • the compositions are administered in an amount and for a time sufficient to maintain immune function in the subject.
  • these compositions are useful in maintaining immune function and therefore promoting or supporting a healthy condition, they (and other compositions described herein) can be administered in conjunction with a diet program and for an exercise-program.
  • compositions can also be taken with meals. Immunity decreases with age, and natural immune responses are adversely affected both as a person ages and in association with numerous conditions. These conditions include the use of immunosuppressant drugs, stress, and various diseases such as cancer, AIDS, hepatitis, and others.
  • the compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides can be used in any circumstance where one wishes to counteract the natural decay of immunity. For example, they can be administered to a generally healthy person. The person may be of a certain age (e.g., a man over fifty years old or a peri- or post-menopausal woman).
  • compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides can also be used to counteract the decrease in immunity that occurs as a side effect of immunosuppressant treatment or in association with cancer and infections (e.g., bacterial, fungal, or viral infections).
  • infections e.g., bacterial, fungal, or viral infections.
  • compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides can be administered to animals (e.g., animals kept as domestic pets, in zoos, or as livestock).
  • animals e.g., animals kept as domestic pets, in zoos, or as livestock.
  • livestock e.g., a cow, sheep, pig, goat, chicken, turkey, duck, or other bird
  • administration of the composition can obviate the need for prophylactic antibiotic treatment.
  • compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides can also be used to treat inflammation in a subject.
  • a composition comprising an anthocyanidin combination rich in delphinidins combined with a composition that comprises andrographolides can be used to treat inflammation.
  • Compositions that are generated from purified or synthesized compounds e.g., mixtures of anthocyanidins and andrographolides
  • the compositions can be administered to a subject (e.g., a human) in an amount and for a time sufficient to inhibit inflammation in the subject.
  • effective dosages can vary based on a number of parameters and particular dosages can be determined by methodologies known in the art. Generally, we expect therapeutically effective amounts of the present compositions or active ingredients therein to vary from about 0.001 mg/kg body weight to about 10 g/kg body weight (e.g., about 0.005, 0.01, 0.05, 0.1, 1.0, 10.0, 100, 250, or 500 mg/kg body weight).
  • the therapeutically effective amount of a composition comprising an anthocyanidin combination rich in delphinidins combined with a composition that comprise andrographolides is at least or about 1 g/kg per body weight (e.g., at least or about 2.5, 5.0, 7.5, or 10.0 g/kg body, weight). These dosages are pertinent regardless of the precise content or intended use.
  • the inflammation can be caused by a variety of conditions or an external injury.
  • the inflammation can be caused by a burn or other traumatic injury, a chemical irritant or toxin, an infection (e.g., a bacterial or viral infection), or an autoimmune disease.
  • compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides can be administered to a subject for the treatment of metabolic syndrome.
  • the composition can be administered in an amount and for a time sufficient to improve a sign or symptom of the metabolic syndrome.
  • the method can include a step of identifying a subject who would be expected to benefit from the administration of a composition.
  • the present method can include a step of performing diagnostic tests and/or patient examinations and/or interviews to determine whether a patient has, or is likely to have, metabolic syndrome and would, therefore, be a candidate for treatment with the compositions just described.
  • Metabolic syndrome is associated with obesity and diabetes.
  • compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides can be used to treat obesity and/or diabetes (e.g., type II diabetes) whether those conditions occur within the context of metabolic syndrome or independent of metabolic syndrome.
  • the compositions comprising anthocyanidin combinations rich in delphinidins combined with compositions that comprise andrographolides can also be used to help regulate cholesterol levels, including the levels of LDL and triglycerides.
  • the present compositions can be used to treat these conditions in the context of metabolic syndrome or independent of that syndrome.
  • the invention features compositions comprising (a) anthocyanidin combinations rich in delphinidins, and (b) compositions that comprise combinations of compounds selected from myrtillin, quercetin, or caffeoyl quinic derivatives and proanthocyanidins.
  • compositions comprising anthocyanidin combinations rich in delphinidins includes an anthocyanidin of the following formula:
  • each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are, independently, —H, —OH, or —OCH 3 , and wherein at least 15% of the anthocyanidins (e.g., at least or about 15%, 20%, 25%, 30%, 40%, 45%, 50%, or more of the anthocyanidins) are delphinidins.
  • the anthocyanidin combination rich in delphinidin can include both delphinidin and cyanidin.
  • compositions comprising anthocyanidin combinations rich in delphinidins can be extracted from a plant of the genus Aristotelia that can be an Aristotelia chilensis plant, and the compositions that comprise combinations of compounds selected from myrtillin, quercetin, or caffeoyl quinic derivatives and proanthocyanidins can be extracted from a plant of the genus Vaccinium that can be, for example, Vaccinium augustifolium and/or Vaccinium myrtillus and/or Vaccinium corimbosum . Other species of Vaccinium can be used, but these are among the most economically viable sources.
  • compositions that comprise combinations of compounds selected from myrtillin, quercetin, or caffeoyl quinic derivatives and proanthocyanidins can be extracted from the herba (the leaves) of a plant of the genus Vaccinium.
  • compositions from a plant of the genus Vaccinium can include myrtillin, quercetin, or a caffeic acid derivative (e.g., chlorogenic acid).
  • a caffeic acid derivative e.g., chlorogenic acid.
  • the content of caffeoylquinic acid can be in the range of 20%.
  • the ratio of the compositions that comprise anthocyanidin combinations rich in delphinidins to the compositions that comprise combinations of compounds selected from myrtillin, quercetin, or caffeoyl quinic derivatives and proanthocyanidins can be about 1.0:0.5 (w:w) to about 1.0:10.0 (w:w).
  • the ratio can be about 1.0:0.1, 1.0:0.5, 1.0:1.0, 1.0:1.5, 1.0:2.0, 1.0:2.5, 1.0:3.0, 1.0:3.5, 1.0:4.0, 1.0:4.5, 1.0:5.0, 1.0:5.5, 1.0:6.0, 1.0:6.5, 1.0:7.0, 1.0:7.5, 1.0:8.0, 1.0:8.5, 1.0:9.0, 1.0:9.5. 1.0:10.0, or 1.0:10.5.
  • these compositions can be prepared from purified or synthesized compounds (e.g., from anthocyanidins and myrtillin, quercetin, or a caffeic acid derivative) rather than extracted from the plant materials per se.
  • the compounds can be formulated for oral administration or consumption.
  • the compositions can further include a carrier or an excipient (e.g., a vegetable oil or animal oil (e.g., fish oil)).
  • a carrier or an excipient e.g., a vegetable oil or animal oil (e.g., fish oil)
  • the compositions can be fashioned using known techniques into tablets, capsules, and the like, for oral administration or incorporated into a food product (e.g., a drink (or beverage) or cereal-type bar).
  • compositions including (a) anthocyanidin combinations rich in delphinidins, and (b) compositions that comprise combinations of compounds selected from myrtillin, quercetin, or caffeoyl quinic derivatives and proanthocyanidins can be administered to a subject for the treatment of metabolic syndrome.
  • the composition can be administered in an amount and for a time sufficient to improve a sign or symptom of the metabolic syndrome.
  • the method can include a step of identifying a subject who would be expected to benefit from the administration of a composition.
  • the present method can include a step of performing diagnostic tests and/or patient examinations and/or interviews to determine whether a patient has, or is likely to have, metabolic syndrome and would, therefore, be a candidate for treatment with the compositions just described.
  • Metabolic syndrome is associated with obesity and diabetes.
  • the compositions that comprise combinations of compounds selected from myrtillin, quercetin, or caffeoyl quinic derivatives and proanthocyanidins can be extracted from a plant of the genus Vaccinium can be used to treat obesity and/or diabetes (e.g., type II diabetes) whether those conditions occur within the context of metabolic syndrome or independent of metabolic syndrome.
  • compositions that comprise combinations of compounds selected from myrtillin, quercetin, or caffeoyl quinic derivatives and proanthocyanidins can be extracted from a plant of the genus Vaccinium can also be used to help regulate cholesterol levels, including the levels of LDL and triglycerides.
  • the present compositions can be used to treat these conditions in the context of metabolic syndrome or independent of that syndrome.
  • compositions can include one or more compounds that are sugar-containing counterparts of an anthocyanidin.
  • compositions can include, in addition to, or in place of, one or more of the anthocyanidins recited herein, a corresponding sugar-containing anthocyanoside flavenoid (also known as an anthocyanin).
  • a corresponding sugar-containing anthocyanoside flavenoid also known as an anthocyanin
  • compositions comprising anthocyanidin combinations can include at least one of delphinidin-3-galactoside; delphinidin-3-glucoside; cyanidin-3-galactoside; delphinidin-3-arabinoside; cyanidin-3-glucoside; petunidin-3-galactoside; petunidin-3-glucoside; cyanidin-3-arabinoside; peonidin-3-galactoside; perunidin-3-arabinoside; malvidin-3-galactoside; peonidin-3-glucoside; malvidin-3-glucoside; peonidin-3-arabinoside; malvidin-3-arabinoside; delphinidin-6-acetyl-3-glucoside; cyanidin-6-acetyl-3-glucoside; malvidin-6-acetyl-3-galactoside; petunidin-6-acetyl-3-galactoside; petunidin-6-acetyl-3
  • the extracts can include at least one of delphinidin 3-sambubioside-5-glucoside; delphinidin 3,5-diglucoside; cyanidin 3-sambubioside-5-glucoside; cyanidin 3,5-diglucoside; delphinidin 3-sambubioside; delphinidin 3-glucoside; cyanidin 3-sambubioside; and cyanidin 3-glucoside.
  • Table 1 shows selected anthocyanidins of formula 1 and their substitutions, any of which can be incorporated into the compositions of the present invention as specified. As noted, an aglycolic counterpart may also be used.
  • compositions can be aqueous compositions.
  • the present compositions can be suspended in lipophilic carriers, which can include vegetable oils (e.g., peanut oil, soybean oil, corn oil, and olive oil) semisynthetic vegetable oils, such as fractionated coconut oil (a medium chain fatty acid triglyceride mixture), unsaturated polyglycolysed glycerides (GPGI) and mineral oil, such as liquid paraffin.
  • vegetable oils e.g., peanut oil, soybean oil, corn oil, and olive oil
  • semisynthetic vegetable oils such as fractionated coconut oil (a medium chain fatty acid triglyceride mixture), unsaturated polyglycolysed glycerides (GPGI) and mineral oil, such as liquid paraffin.
  • GPGI medium chain fatty acid triglyceride mixture
  • mineral oil such as liquid paraffin.
  • animal oils, including fish oils can also be used. Regardless of the precise source, the oils can also be those that are rich in unsaturated omega-3 fatty acids and phospholipids.
  • Suspensions can be prepared by suspending micronized extracts in the carrier (e.g., by stirring at room temperature).
  • Conventional rheological modifiers can also be added to optimize the physical stability of the suspensions, as well as conventional surfactants (which we may refer to more generally as a carrier or excipient), such as soybean lecithin, to ensure a good wettability.
  • the resulting oily suspensions can then be directly distributed in gelatine capsules or absorbed on suitable excipients, such as colloidal silicon dioxide, starch or mannitol.
  • suitable excipients such as colloidal silicon dioxide, starch or mannitol.
  • kneads can be obtained that are granulated and distributed in sachets or used for preparing tablets.
  • compositions of the present invention may be present in the compositions of the present invention and will also improve their effects.
  • the upper limit can be no more than 50%, 60%, 70%, 75%, 80%, 85%. or 90%.
  • the anthocyanidin content can be at least 5% (e.g., 30%) but less than 80% of the extract (w/w).
  • compositions described herein work synergistically.
  • compositions comprising anthocyanidin combinations combined with the compositions comprising andrographolides or with the compositions that comprise combinations of compounds selected from myrtillin, quercetin, or caffeoyl quinic derivatives and proanthocyanidins an effect that is greater than one would expect from simply combining the two compositions; they are not simply additive.
  • compositions described herein may also include some diterpenes. As these compounds have immunostimulatory effects, they may be included in any of the present compositions.
  • compositions can be extracted from the aforementioned plants.
  • the extracts of the selected plants can be prepared according to processes that are known and used in the art to prepare botanical extracts.
  • the processes can be standardized to improve reproducibility and consistency from extract to extract.
  • the processes can begin with ripe fruits, fresh or frozen, or, where specified, the herba of a plant. Extraction can proceed in ethanol in the presence of organic or mineral acids or by extracting the fruits with water in the presence of bisulfite ions. See J. B. Hrborne, The flavonoids, Chapman & Hall Ed. London p 227.
  • the bisulfite ions may be prepared by methods known in the art (e.g., by the addition of sulfur dioxide or simply by addition of sodium methabisulfite).
  • the ratio between the fruits and water containing methabisulfite is 1:10 and the ratio between anthocyanosides and sodium bisulfite in molarity is 1:3.
  • the solution of bisulfite adducts whose pH generally ranges from 1 to 3.5 can then be alkalinized until the pH reaches 5 and subsequently eluted through a column containing non-ionogenic polymeric resins. While in acidic conditions, the anthocyanoside-bisulfite adducts can be absorbed with other polyphenols present in the extract at pH 5. The bisulfite adducts remain surprisingly in solution whereas the other phenolics are absorbed and so separated from the anthocyanosides.
  • the extract may not be alkanized and passed directly on the resin at acid pH; after absorption of the compounds the column can be eluted with water in order to eliminate salts and sugar and inert compounds.
  • the resin is washed with ethanol for the recovery of the polyphenolic substances including the anthocyanosides as bisulfite adducts.
  • the alcoholic solution can be concentrated under vacuum at a temperature ranging between about 25 and 40° C. (e.g., 35° C.) until half of the volume of the weight fruits is achieved.
  • the concentrate can then be acidified with diluted acid (e.g., hydrochloric acid) under stirring in a nitrogen-rich atmosphere to remove sulphur dioxide.
  • diluted acid e.g., hydrochloric acid
  • the gas flow can be bubbled in a sodium hydroxide aqueous solution to avoid sulphur dioxide pollution in the environment.
  • the concentrate containing all of the phenolic substances could be evaporated to dryness.
  • the concentrate can be alkalinized at pH 6 and extracted with n-butanol or ethyl acetate to remove the procyanidins and tannin-like substances.
  • the solution can then be acidified with hydrochloric acid to remove sulphur dioxide as described above.
  • the anthocyanoside content in the extract in this case is in the range of 90-95%.
  • the dried leaves can be extracted after grinding with a mixture of water miscible alcohols (e.g., ethanol with water, such as ethanol/water 50% v/v) until the extractable substances are fully recovered.
  • a mixture of water miscible alcohols e.g., ethanol with water, such as ethanol/water 50% v/v
  • the combined hydro-alcoholic extracts are concentrated to water filtering at this point cloudy precipitates and fine particles of leaves etc.
  • the resin can be eluted with water to largely eliminate undesired substances like sugars, peptides, and salts, and the active principle can then be eluted with ethanol 95% until the exhaustion or the same.
  • the ethanolic eluate can be concentrated under vacuum at a temperature not to exceed about 40° C.
  • the content of andrographolide would be expected to be in the range of 30 and 40% depending on certain factors such as the original content in the leaves.
  • This extract could be used as it is or in combination with the purified extract of Aristotelis chilensis or another anthocyanidin-containing plant.
  • the anthocyanins are subdivided into the sugar-free anthocyanidin aglycones and the anthocyanin glycosides, and the compositions of the present methods can include either or both of types of anthocyanins.
  • the therapeutically effective amount of an individual anthocyanin or of a particular anthocyanin or other active compound in the present compositions can vary from about 0.01 mg/kg body weight to about 1 g/kg body weight.
  • the anthocyanin component of the present compositions can include one or more of delphinidin-3-galactoside; delphindin-3-glucoside; cyanidin-3-galactoside; delphinidin-3-arabinoside; cyanidin-3-glucoside; petunidin-3-galactoside; petunidin-3-glucoside; cyanidin-3-arabinoside; peonidin-3-galactoside; perunidin-3-arabinoside; malvidin-3-galactoside; peonidin-3-glucoside; malvidin-3-glucoside; peonidin-3-arabinoside; malvidin-3-arabinoside; delphinidin-6-acetyl-3-glucoside; cyanidin-6-acetyl-3-glucoside; malvidin-6-acetyl-3-galactoside; petunidin-6-acetyl-3-galactoside; peonidin-6-acetyl-3
  • the active agent may be, for example, but is not limited to, at least one of a flavonoid or an anthocyanin, or a derivative or variant thereof, an anthocyanin of blueberry such as, for example, delphinidin-3-galactoside; delphindin-3-glucoside; cyanidin-3-galactoside; delphinidin-3-arabinoside; cyanidin-3-glucoside; petunidin-3-galactoside; petunidin-3-glucoside; cyanidin-3-arabinoside; peonidin-3-galactoside; perunidin-3-arabinoside; malvidin-3-galactoside; peonidin-3-glucoside; malvidin-3-glucoside; peonidin-3-glucoside; peonidin-3-glucoside; peonidin-3-glucoside; peonidin-3-glucoside; peonidin-3-galcoside; peonidin-3-galcoside;
  • Extract refers to the process of drawing out, withdrawing, distilling or otherwise separating one substance from another by a chemical or physical process.
  • the extract can be a solid, viscid, or liquid substance extracted from a plant or, for example, a mixed population of synthetic compounds, or the like, containing its essence in concentrated form.
  • carrier as a “drug carrier”, “carrier”, or “vehicle,” and these terms refer to carrier materials suitable for administration of the anthocyanin compounds as described herein, or variants or derivatives thereof.
  • Carriers useful in the present compositions include many materials known in the art that are nontoxic and do not actively interact with other components (i.e., they are considered inert).
  • a “pharmaceutically acceptable carrier” is any substantially non-toxic carrier conventionally used in pharmaceuticals that may improve the stability or bioavailability of the active agent.
  • Useful carriers include esterified glycerides, which may be saturated or unsaturated.
  • Useful carriers also include polyethylene glycol and fatty acids.
  • the pharmaceutical compositions of the invention can also include suitable solid or gel phase carriers or excipients (e.g., calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycol, as mentioned above).
  • the present pharmaceutical compositions can be microencapsulated, and if appropriate, with one or more excipients, encochleated, coated onto microscopic gold particles, contained in liposomes, pellets for implantation into the tissue, or dried onto an object to be rubbed into the tissue.
  • the present pharmaceutical compositions also may be in the form of granules, beads, powders, tablets, coated tablets, (micro)capsules, suppositories, syrups, emulsions, suspensions, creams, drops or preparations with protracted release of active compounds, in whose preparation excipients and additives and/or auxiliaries such as disintegrants, binders, coating agents, swelling agents, lubricants, or solubilizers are customarily used as described above.
  • the pharmaceutical compositions are suitable for use in a variety of drug delivery systems.
  • the anthocyans described herein may be delivered in the form of a pharmaceutically acceptable salt.
  • the salts should be pharmaceutically acceptable, but non-pharmaceutically acceptable salts may conveniently be used to prepare pharmaceutically acceptable salts thereof.
  • Such salts include, but are not limited to, those prepared from the following acids: hydrochloric, hydrobromic, sulphuric, nitric, phosphoric, maleic, acetic, salicylic, p-toluene sulphonic, tartaric, citric, methane sulphonic, formic, malonic, succinic, naphthalene-2-sulphonic, and benzene sulphonic.
  • salts may be prepared as alkaline metal or alkaline earth salts, such as sodium, potassium or calcium salts of the carboxylic acid group.
  • pharmaceutically acceptable salt is meant those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit/risk ratio.
  • the salts may be prepared in situ during the final isolation and purification of the compounds described within the present invention or separately by reacting a free base function with a suitable organic acid.
  • Representative acid addition salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate(isethionate), lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, phosphate, glutamate, bicarbonate, p-toluenesulfonate and undecanoate
  • the basic nitrogen-containing groups may be quaternized with such agents as lower alkyl halides such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl and diamyl sulfates; long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides; arylalkyl halides like benzyl and phenethyl bromides and others. Water or oil-soluble or dispersible products are thereby obtained.
  • lower alkyl halides such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides
  • dialkyl sulfates like dimethyl, diethyl, dibutyl and diamyl sulfates
  • long chain halides such as decyl
  • Basic addition salts may be prepared in situ during the final isolation and purification of compounds described within the invention by reacting a carboxylic acid-containing moiety with a suitable base such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation or with ammonia or an organic primary, secondary or tertiary amine.
  • Pharmaceutically acceptable salts include, but are not limited to, cations based on alkali metals or alkaline earth metals such as lithium, sodium, potassium, calcium, magnesium and aluminum salts and the like and nontoxic quaternary ammonia and amine cations including ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine and the like.
  • Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine and the like.
  • salts may be also obtained using standard procedures well known in the art, for example by reacting a sufficiently basic compound such as an amine with a suitable acid affording a physiologically acceptable anion.
  • a sufficiently basic compound such as an amine
  • a suitable acid affording a physiologically acceptable anion.
  • Alkali metal for example, sodium, potassium or lithium
  • alkaline earth metal for example calcium or magnesium
  • the formulations may be presented conveniently in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing into association a sugar-free anthocyanidin aglycone and/or an anthocyanin glycoside, or a derivative or variant thereof, with the carrier that constitutes one or more accessory agents. In general, the formulations are prepared by uniformly and intimately bringing into association the active agent with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation.
  • anthocyanins and anthocyanidins as described herein, or a pharmaceutically acceptable ester, salt, solvate or prodrug thereof may be mixed with other active materials that do not impair the desired action, or with materials that supplement the desired action (e.g., the andrographolides described herein).
  • Solutions or suspensions used for parenteral, intradermal, subcutaneous, intrathecal, or topical application may include, but are not limited to, for example, the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose.
  • the parental preparation may be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. Administered intravenously, particular carriers are physiological saline or phosphate buffered saline (PBS).
  • PBS physiological saline or phosphate buffer
  • Example 1 Preparation of A. chilensis Extract Containing Anthocyanidins and Polyphenols
  • Frozen fruits of Aristotelia chilensis (1 kg) containing 15 g of anthocyanidins were extracted with 5 ⁇ 1 L of ethanol/water, 50% v/v; each extraction was carried out for 4 hours.
  • 7.5 g of sodium bisulfite were dissolved in the ethanol/water solvent.
  • the extracted liquids were concentrated under vacuum at a temperature of 30° C. to a volume of 2 Lin order to eliminate the ethanol.
  • the concentrate was loaded on to a column of 2.5 L of a non-polar polystyrenic resin having a particle size of 25-60 mesh. The column was washed with 10 L of water and then washed with 3 L of ethanol (95%).
  • the ethanolic solution was concentrated to 0.5 L (essentially removing the ethanol) with stirring, and the concentrated solution was acidified to pH 1 in a current of nitrogen to remove the SO 2 , by bubbling into an NaOH solution. The dark red solution was then carefully concentrated under vacuum to dryness. 150 g of extract was obtained with an anthocyanidin content of about 30%.
  • An Aristotelia chilensis extract containing both anthocyanidins and polyphenols was prepared essentially according to themethod in Example 1, except that the ethanolic solution was concentrated to 1 L and, after acidification, was diluted to 2.5 L with water and loaded onto a 2 L polystyrene column as described in Example 1. The column was eluted with ethanol as described. With this process, the yield of the extract was about 135 grams and included about 41% anthocyanidins.
  • Example 3 Preparing an Extract with High Content of Anthocyanidins from A. chilensis
  • Frozen fruits of Aristotelia chilensis (1 kg) containing 15 g of anthocyanidins were extracted with 5 ⁇ 1 L of ethanol/water 50% v/v. Each extraction was carried out for 4 hours.
  • 7.5 g of sodium bisulfite were dissolved in the ethanol/water solvent.
  • the extracted liquids were concentrated under vacuum at a temperature of 30° C. to a volume of 2 Lin order to eliminate the ethanol.
  • the mixture was alkalinized to pH 5.5 by addition of a 10% solution of NaOH and loaded on a column containing 2 L of non-polar polystyrenic resins. The column was eluted with 2 L of water.
  • the aqueous eluate was then concentrated to 2 L and acidified to pH 1 by addition of hydrochloric acid and then loaded on another 2 L column of a non-polar polystyrenic resin.
  • We continued washing with water until the eluate was colourless.
  • Anthocyanidins were recovered from the resin by washing with ethanol until the ethanol was colourless.
  • the alcoholic solution was concentrated to dryness, yielding 50 g of an extract containing 95% anthocyanidins.
  • Example 5 An Extract with a High Content in Caffeoyl Esters of Quinic Acid and Proanthocyanidins
  • Example 6 Delphinidin Induced Intracellular Calcium Release in a Dose-Dependent Manner
  • HBSS Hanks' Balanced Salt Solution
  • FURA 2-AM Fura-2-acetoxymethyl ester
  • the fluxes of Ca 2+ were measured as ratio of excitation at 340 and 380 nm, and emission at 509 nm, for 300 seconds, at 37° C. in a spectrofluorimeter (LS55, PerkinElmer).
  • the area under the curve (AUC) of the ratio of excitation of 340 to 380 nm, and emission at 509 nm during 300 seconds after treatments varied with the delphinidin concentration.
  • the area under the curve was 66.7%, 275% and 316.7% higher, respectively, than that obtained for untreated control cells.
  • FURA 2-AM-loaded Jurkat T cells were incubated in HBSS calcium free medium as decribed in Example 6.
  • the cells were incubated in 50 uM delphinidin, or in 50 uM delphinidin and 10 ⁇ M N-[4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP-2, a Store-Operated Calcium Entry (SOCE) inhibitor).
  • BTP-2 Store-Operated Calcium Entry
  • the release of Ca 2+ was measured as ratio of excitation at 340 and 380 nm, and emission at 509 nm, for 200 seconds, at 37° C., in a spectrofluorimeter (LS55, PerkinElmer).
  • both the samples treated with delphinidin alone and the samples treated with delphinidin plus 10 uM BTP-2 generated a peak of the excitation ratio at 340 and 380 nm, and emission at 509 nm.
  • the area under the curve (AUC) for the samples incubated in delphinidin alone and in dephinidin plus 10 uM BTP-2 was 1700% and 1566% higher, respectively, than that of the untreated control cells.
  • the area under the curve for the samples incubated in delphinidin alone and with dephinidin plus 10 uM BTP-2 was 184.2% and 100%, respectively, of the value obtained for the untreated control cells.
  • FURA 2-AM-loaded Jurkat T cells were incubated in HBSS calcium free medium. The cells were then incubated in 50 uM delphinidin and the fluxes of Ca 2+ were measured as ratio of excitation at 340 and 380 nm, and emission at 509 nm, at 37° C. in a spectrofluorimeter (LS55, PerkinElmer).
  • Example 9 Delphinidin Induced Cellular Activation Via Store Operated Calcium Influx
  • FURA 2-AM-loaded Jurkat T cells were incubated in HBSS calcium free medium. The cells were incubated in 50 uM delphinidin or 50 uM delphinidin plus 10 ⁇ M BTP-2 and the fluxes of Ca 2+ were measured as ratio of excitation at 340 and 380 nm, and emission at 509 nm, at 37° C. in a spectrofluorimeter (LS55, PerkinElmer).
  • FIG. 2A shows the spectrofluorescence results for the average of 4 measurements of calcium fluxes in Jurkat T cells incubated in delphinidin 50 ⁇ M.
  • FIG. 2B shows the spectrofluorescence results for the average of 4 measurements of calcium fluxes in Jurkat T cells incubated in delphinidin 50 ⁇ M plus BTP-2 10 ⁇ M.
  • the delphinidin-induced calcium influx shown in FIG. 2A , was reduced in the presence ( FIG. 2B ) of the Store-Operated Calcium Entry (SOCE) inhibitor, BTP-2.
  • SOCE Store-Operated Calcium Entry
  • PLC phospholipase C
  • Jurkat T cells in RPMI medium were incubated for 48 hrs at 37° C., in 5% CO 2 in the presence of vehicle control solution; or the T cell activator, phorbol 12-myristate 13-acetate/lonomycin (PMA/Io 2 ng/ml 1 uM); 50 ⁇ M of delphinidin; 50 ⁇ M delphinidin+PMA/Io; 50 ⁇ M cyanidin; or 50 ⁇ M cyaniding+PMA/Io. Then the supernatants were collected and IL-2 production was analyzed by ELISA using a commercial kit (Becton Dickinson, USA) according to the supplier's directions.
  • PMA/Io 2 ng/ml 1 uM phorbol 12-myristate 13-acetate/lonomycin
  • 50 ⁇ M of delphinidin 50 ⁇ M delphinidin+PMA/Io
  • 50 ⁇ M cyanidin 50 ⁇ M cyaniding+PMA
  • delphinidin-treated cells produced significantly (P ⁇ 0.05) higher levels of IL-2 (240% higher) than did the untreated control cells, while the cyanidin-treated cells produced slightly less IL-2 (10%) lower than did the control cells.
  • INF- ⁇ production in samples of Jurkat T cells with different treatments Average INF- ⁇ Percentage vs. Treatment production [pg/ml] control [%] Control samples 8 100 PMA/Io 60 750 50 ⁇ M delphinidin 28 350 50 ⁇ M delphinidin + PMA/Io 125 1562.5 50 ⁇ M cyanidin 8 100 50 ⁇ M cyaniding + PMA/Io 110 1375
  • delphinidin-treated cells produced significantly (P ⁇ 0.05) higher levels of INF- ⁇ (250% higher) than did the untreated control cells, while the cyanidin-treated cells produced about the same levels of INF- ⁇ as did the control cells.
  • the positive control PMA/Io induced high levels of INF- ⁇ production.
  • the compounds showed a syngergistic effect in INF- ⁇ production, i.e., the levels of INF- ⁇ were about twice that of cells treated with PMA/Io alone.
  • Example 13 Delphinidin Induced IL-2 and INF- ⁇ in Human T Cells Via SOCE
  • the effect of delphinidin on IL-2 and INF- ⁇ production was also assayed on freshly isolated human T cells.
  • Human T cells were isolated from blood of healthy volunteers using Lymphoprep reagent. T cells (1 ⁇ 10 6 ) in RMPI medium were incubated for 48 hrs at 37° C., in 5% CO 2 in the presence of a vehicle control solution; 50 ⁇ M delphinidin; 50 ⁇ M delphinidin+1 ⁇ M BTP-2; 50 ⁇ M delphinidin+5 ⁇ M BTP-2; 50 ⁇ M delphinidin+10 ⁇ M BTP-2; 1 ⁇ M BTP-2; 5 ⁇ M. BTP-2; or 10 ⁇ M BTP-2. Then the supernatants were collected and analyzed using commercial ELISA kit (Becton Dickinson, USA) to measure IL-2 and INF- ⁇ production according to the supplier's directions.
  • Treatment Average IL-2 production [pg/ml] Control samples 0 50 ⁇ M delphinidin 370 50 ⁇ M delphinidin + 1 ⁇ M BTP-2 23 50 ⁇ M delphinidin + 5 ⁇ M BTP-2 20 50 ⁇ M delphinidin + 10 ⁇ M BTP-2 10 1 ⁇ M BTP-2 0 5 ⁇ M BTP-2 0 10 ⁇ M BTP-2 0
  • delphinidin-treated human T cells produced significantly higher levels of IL-2 than did the untreated control cells.
  • BTP-2 significantly (P ⁇ 0.05) reduced the delphinidin-induced production of IL-2 at all concentrations tested.
  • BTP_2 treatment alone did not induce IL-2 production.
  • delphinidin-treated human T cells produced significantly (P ⁇ 0.05) higher levels (950% higher) of INF- ⁇ than did the untreated control cells.
  • BTP-2 showed a dose-dependent reduction in the delphinidin-induced production of INF- ⁇ at all concentrations tested.
  • BTP_2 treatment alone did not induce IL-2 production.
  • Example 14 Delphinidin Induced IL-2 Production Via Nuclear Factor of Activated T Cells (NFAT) Activation
  • Jurkat T cells were incubated in either a vehicle control solution; 5 nM andrographolide; 50 ⁇ M delphinidin; or 5 nM andrographolide plus 50 ⁇ M delphinidin.
  • delphinidin-treated Jurkat T cells produced higher levels (39.4% higher) of IL-2 than did the untreated control cells; a slight reduction was observed with adrographolide.
  • the two compounds showed a syngergistic effect in IL-2 production, i.e., the levels of IL-2 were 127% higher that those of cells treated with either andrographolide and delphinidin alone.
  • HL-60 cells Human promyelocytic leukemia cells.
  • HL-60 cells in IMDM medium were transfected with a reporter vector with an NF-kB consensus sequence located in the luciferase promoter for 24 h at 37° C., then were incubated with delphinidin-rich anthocyanidins diluted 1:500000, 1:50000, and 1:5000.
  • PMA was used as positive control.
  • Luciferase activity was measured with a Dual luciferase assay kit (Promega) according to the supplier's instructions.
  • a vector that constitutively expressed renilla luciferase was used to standardize the assay.
  • HL-60 luciferase transfectants showed a significant dose-dependent decrease in luciferase activity (at least three independent experiments, with a P ⁇ 0.05). These data suggested that the activity of the anthocyanidins rich in delphinidins was mediated by NF- ⁇ B.
  • composition comprising anthocyanidins rich in delphinidins was prepared according to the present invention.
  • COX-2 cyclooxygenase 2
  • Caco-2 cells a tumor line of colon cancer that constitutively expresses COX-2
  • MEM medium a tumor line of colon cancer that constitutively expresses COX-2
  • levels of COX-2 mRNA were analyzed by real-time RT_PCR using COX-2 specific primers using SYBRGreen reagent (Stratagene); ⁇ -actin served as an internal control.
  • Levels of COX-2 protein were assayed by immunoblotting using a specific COX-2 antibody (Cayman) was performed to compare the expression; ⁇ -actin was used as standardized control.
  • FIG. 4A shows COX-2 polypeptide levels in an immunoblot of CaCo-2 cells treated with 1.75 ⁇ g/ml of delphinidin-rich anthocyanidins after 0, 24, 48, and 72 hrs.
  • FIG. 4B shows COX-2 mRNA levels in CaCo-2 cells treated with 1.75 ⁇ g/ml of delphinidin-rich anthocyanidins for 24 hrs.
  • treatment with 1.75 ⁇ g/ml of delphinidin-rich anthocyanidins for 24 hours reduced COX-2 polypeptide levels by about 50%; further reduction was observed at 48 and 72 hours.
  • treatment with 1.75 ⁇ g/ml of delphinidin-rich anthocyanidins for 24 hours significantly reduced COX-2 mRNA levels to 50% of control levels.
  • PPar- ⁇ peroxisome proliferator-activated receptor, a receptor involved in sensitization to insulin
  • HL-60 cells in IMDM medium were transfected with the reporter vectors PPAR- ⁇ -Luc (5 ⁇ g) (Panomics) and TK-RL (1 ⁇ g) (Promega) using Fugene 6 reagent (Roche), and cultured for 24 hr.
  • the cells were incubated for 12 h in 0.175, 1.75, or 17.5 ⁇ g/ml of delphindin-rich anthocyanidins, phorbol myristate acetate (PMA), 15-deoxi-d 12,14-prostaglandin J2 (PGj2), or tumor necrosis factor alpha (TNF ⁇ ) as controls.
  • PMA phorbol myristate acetate
  • PGj2 15-deoxi-d 12,14-prostaglandin J2
  • TNF ⁇ tumor necrosis factor alpha
  • the hyperglycemic rats were randomly assigned to different groups: a water-treated control group, a group treated with 7 mg/kg of delphinidin-rich anthocyanidins; and group treated with 70 mg/kg of delphinidin-rich anthocyanidins. Each group consisted of 5 rats. The rats were treated for two weeks with the delphinidin-rich anthocyanidins mixed in the drinking water of the rats. After two weeks of treatment, 1 ml of blood was obtained from each animal by retro-orbital puncture. The glycemia level was determined in the blood with glucose oxidase method (Wiener-Lab).
  • Example 21 Formulation of a Composition Comprising Delphinidin-Rich Anthocyanidins into Hard Gelatin Capsules
  • composition comprising anthocyanidins (41% anthocyanidins, 400 mg 35% of this anthocyanidins are delphinidins)
  • Microcrystalline cellulose 400 mg Lactose 95 mg Silicon dioxide 10 mg
  • the invention encompasses similar compositions in which the amounts provided for one or more of the components vary, for example, by plus-or-minus about 10%.
  • the invention encompasses compositions comprising the components listed above in which, for example, the anthocyanin/anthocyanidin is present at 360-440 mg.
  • Example 22 Formulation of a Composition Comprising Andrographolides and Delphinidin-Rich Anthocyanidins (Ratio 3:1) into an Oily Suspension for Soft Cellulose Capsules
  • Composition comprising andrographolides 300 mg (35% total andrographolides) Composition comprising anthocyanidins (41% anthocyanidins, 100 mg 35% of this anthocyanidins are delphinidins) Glyceryl monostearate 30 mg Soya lecithin 20 mg Oenothera biennis oil q.s. for 700 mg
  • Example 23 Formulation of a Composition Including a Composition Comprising Andrographolides and Delphinidin-Rich Anthocyanidins (Ratio 3:1) into Hard Gelatin Capsules
  • composition comprising andrographolides 300 mg (35% total andrographolides) Composition comprising anthocyanidins (41% anthocyanidins, 100 mg 35% of this anthocyanidins are delphinidins) Microcrystalline cellulose 400 mg Lactose 95 mg Silicon dioxide 10 mg
  • Example 24 Formulation of a Composition Comprising Andrographolides and Delphinidin-Rich Anthocyanidins (Ratio 1:1) into Hard Gelatin Capsules
  • composition comprising andrographolides 200 mg (35% total andrographolides)
  • Composition comprising anthocyanidins (41% anthocyanidins, 200 mg 35% of this anthocyanidins are delphinidins)
  • Microcrystalline cellulose 400 mg Povidone 15 mg Sodium carboxymethylcellulose 10 mg
  • Example 25 Formulation of a Composition Comprising Delphinidin-Rich Anthocyanidins and a Caffeeoylquinic Acid (Ratio 1:1) into Hard Gelatin Capsules
  • composition comprising caffeeoylquinic acid 200 mg (20% cafeeoylquinic acid)
  • Composition comprising anthocyanidins (41% anthocyanidins, 200 mg 35% of this anthocyanidins are delphinidins)
  • Microcrystalline cellulose 400 mg Lactose 95 mg Silicon dioxide 10 mg
  • the Maqui extract was standardized extract of fresh maqui fruit (35% of total anthocianins, min: total delphinidins 25%: min. delphinidin DSG: 5%); the A. paniculata extract was from dried herba (37% total andrographolides, with approximately 20 to 40% w/w of Andrographolide, about 5 to 10% w/w of 14-Deoxyandrographolide, and about 0.2 to 0.8% w/w of Neoandrographolide.
  • Vaccinium angustifolium extract was a: standardized extract of dried leaves (chorogenic acid 16%).
  • the botanical extracts that include an anthocyanidin can be made from any botanical that includes such compounds (e.g., plants of the genus Ribes, Vitis , and Sambucus , as well as the Aristotelia and Vaccinium plants described at length above). Accordingly, other embodiments are within the scope of the invention and the following claims.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Emergency Medicine (AREA)
  • Diabetes (AREA)
  • Botany (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • Dermatology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Transplantation (AREA)
  • Endocrinology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Toxicology (AREA)
US13/076,117 2009-10-21 2011-03-30 Compositions that include anthocyanidins and methods of use Active 2035-02-07 US10786522B2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US13/076,117 US10786522B2 (en) 2009-10-21 2011-03-30 Compositions that include anthocyanidins and methods of use
US14/587,070 US20150164932A1 (en) 2009-10-21 2014-12-31 Compositions That Include Anthocyanidins and Methods of Use
US16/256,384 US20190151342A1 (en) 2009-10-21 2019-01-24 Compositions that include anthocyanidins and methods of use

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US25383509P 2009-10-21 2009-10-21
US27954109P 2009-10-22 2009-10-22
PCT/IB2010/002698 WO2011048479A2 (en) 2009-10-21 2010-10-21 Compositions that include anthocyanidins and methods of use
US13/076,117 US10786522B2 (en) 2009-10-21 2011-03-30 Compositions that include anthocyanidins and methods of use

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2010/002698 Continuation WO2011048479A2 (en) 2009-10-21 2010-10-21 Compositions that include anthocyanidins and methods of use

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US14/587,070 Continuation US20150164932A1 (en) 2009-10-21 2014-12-31 Compositions That Include Anthocyanidins and Methods of Use

Publications (2)

Publication Number Publication Date
US20110268825A1 US20110268825A1 (en) 2011-11-03
US10786522B2 true US10786522B2 (en) 2020-09-29

Family

ID=43709162

Family Applications (3)

Application Number Title Priority Date Filing Date
US13/076,117 Active 2035-02-07 US10786522B2 (en) 2009-10-21 2011-03-30 Compositions that include anthocyanidins and methods of use
US14/587,070 Abandoned US20150164932A1 (en) 2009-10-21 2014-12-31 Compositions That Include Anthocyanidins and Methods of Use
US16/256,384 Abandoned US20190151342A1 (en) 2009-10-21 2019-01-24 Compositions that include anthocyanidins and methods of use

Family Applications After (2)

Application Number Title Priority Date Filing Date
US14/587,070 Abandoned US20150164932A1 (en) 2009-10-21 2014-12-31 Compositions That Include Anthocyanidins and Methods of Use
US16/256,384 Abandoned US20190151342A1 (en) 2009-10-21 2019-01-24 Compositions that include anthocyanidins and methods of use

Country Status (7)

Country Link
US (3) US10786522B2 (sv)
EP (1) EP2344154B1 (sv)
JP (2) JP2013508347A (sv)
KR (1) KR101625882B1 (sv)
CA (1) CA2735343A1 (sv)
ES (1) ES2618952T3 (sv)
WO (1) WO2011048479A2 (sv)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023150072A1 (en) 2022-02-01 2023-08-10 Sinclair David A Compositions and methods for the preservation of plant matter

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5968610B2 (ja) * 2011-10-24 2016-08-10 株式会社ファイン マクイベリー含有抗酸化組成物
US11753617B2 (en) 2011-11-02 2023-09-12 Texas Tech University System Media compositions for promoting bacterial and fungal growth
ES2715984T3 (es) * 2011-11-02 2019-06-07 Univ Texas Tech System Composiciones de caldos para promover el desarrollo bacteriano y el crecimiento fúngico
CA2857368C (en) 2011-12-16 2015-09-08 Centre De Recherche Industrielle Du Quebec Method for extracting anthocyanin derivatives from a plant source
CN104302183B (zh) * 2012-03-30 2017-03-01 赛博尔泰克股份公司 飞燕草色素对抗金黄色葡萄球菌的应用
JP2013234140A (ja) * 2012-05-08 2013-11-21 Oriza Yuka Kk 発毛促進剤
CN102716122B (zh) * 2012-07-03 2014-06-25 郑州大学 15-苄亚基-14-脱氧-11,12-脱氢穿心莲内酯衍生物在制备治疗糖尿病药物中的应用
EP2682005A1 (en) 2012-07-05 2014-01-08 Symrise AG A dietary supplement composition
CN102786507B (zh) * 2012-08-27 2014-12-10 袁乃坤 从紫色马铃薯中快速提取食品级花青素的简便方法
US20140128333A1 (en) * 2012-11-02 2014-05-08 Maqui New Life S.A. Compounds, Compositions, and Methods for Decreasing Intestinal Glucose Uptake and Inducing Incretin Release
DK2919791T3 (da) * 2012-11-15 2017-07-17 Sapiotec Gmbh Delphinidin-kompleks som antiflogistisk eller immunsuppressivt aktivt stof
CA2893883A1 (en) 2012-12-11 2014-06-19 Sapiotec Gmbh Delphinidin for combating melanoma cells
WO2014098092A1 (ja) * 2012-12-18 2014-06-26 オリザ油化株式会社 ドライアイ予防・治療剤
US10016380B2 (en) 2013-05-01 2018-07-10 Lanny Leo Johnson Antimicrobials and methods of use thereof
US10398664B2 (en) 2013-05-01 2019-09-03 Lanny Leo Johnson Methods of diagnosing and treating infected implants
WO2014179318A2 (en) 2013-05-01 2014-11-06 Johnson Lanny Leo Antimicrobials and methods of use thereof for wound healing
JP6144536B2 (ja) * 2013-05-14 2017-06-07 オリザ油化株式会社 美白剤
WO2014186369A1 (en) * 2013-05-15 2014-11-20 Abbott Laboratories Nutritional composition comprising anthocyanidin(s) and related methods
CN103766901A (zh) * 2014-01-08 2014-05-07 浙江大学 一种穿心莲丙素在制备减肥食品或药品中的应用
JP2015182955A (ja) * 2014-03-20 2015-10-22 学校法人中部大学 Ｇｌｐ−１分泌促進剤
JP6742575B2 (ja) * 2015-07-02 2020-08-19 株式会社東洋新薬 関節機能改善組成物
CN105017202A (zh) * 2015-08-11 2015-11-04 贵州北极熊实业有限公司 一种从黑莓果渣中提取花青素的方法
ITUA20161822A1 (it) * 2016-03-18 2017-09-18 Indena Spa Composizioni utili nella prevenzione e/o nel trattamento di patologie del cavo orale, delle prime vie aeree e dell’esofago
IT201700040937A1 (it) * 2017-04-12 2018-10-12 Giannamaria Annunziato Antocianidine per il trattamento e la prevenzione di malattie infiammatorie e metaboliche
KR102032621B1 (ko) 2017-12-01 2019-10-15 숙명여자대학교산학협력단 마키베리 추출물 또는 이의 효소 가수분해물을 유효성분으로 함유하는 갱년기 증상 예방 또는 치료용 약학적 조성물
CN108853026A (zh) * 2018-08-21 2018-11-23 无锡正大生物股份有限公司 一种兽用穿心莲内酯散
MX2018011698A (es) * 2018-09-26 2019-08-27 Instituto Nac De Enfermedades Respiratorias Ismael Cosio Villegas Uso de inhibidores enzimaticos de cd38 en pacientes vih positivos.
EP3701960A1 (en) * 2019-02-27 2020-09-02 Anklam Extrakt GmbH Maqui berry extracts for use in the treatment or prevention of bone disorders
US20220220087A1 (en) * 2019-04-23 2022-07-14 Francis Michelle Mann Anthocyanin extraction methods
EP3733194A1 (en) * 2019-05-03 2020-11-04 Anklam Extrakt GmbH Maqui berry extracts for treatment of skin diseases
KR102153250B1 (ko) * 2020-01-10 2020-09-07 건국대학교 글로컬산학협력단 클로로겐산을 표준물질로 함유하는 블루베리의 항염증 조성물
EP4199752A1 (en) * 2020-08-24 2023-06-28 Neuroscience Pharma SpA Fruit extracts for use in the treatment of neurodegenerative diseases
CN112220704B (zh) * 2020-09-29 2023-01-31 四川大学华西医院 一种天然高spf防晒剂及其制备方法和在彩妆中的应用
KR102575617B1 (ko) * 2020-12-22 2023-09-06 안동대학교 산학협력단 상동나무 추출물을 유효성분으로 포함하는 면역증진용 조성물
US20220257692A1 (en) * 2021-02-17 2022-08-18 Plexus Worldwide, Llc Compositions and methods for supporting immune health
KR20220122877A (ko) * 2021-02-26 2022-09-05 유한회사 한터 블랙커런트 열수 추출물을 포함하는 비알코올성 지방간 질환의 예방, 개선 또는 치료용 조성물
WO2022211649A1 (en) * 2021-04-02 2022-10-06 Aronpharma Sp. Z O.O. Pharmaceutical composition and its antiviral use
RS20210431A1 (sr) 2021-04-07 2022-10-31 Phytonet Doo Ekstrakti aristotelia chilensis u tretmanu gljivičnih infekcija
KR102598567B1 (ko) * 2023-02-24 2023-11-07 재단법인 전남바이오진흥원 가시모밀 추출물을 유효성분으로 포함하는 면역증강용 건강기능식품 조성물

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997041137A1 (en) 1996-04-17 1997-11-06 Unifob Use of anthocyanidin and anthocyanidin derivatives
EP1074254A2 (en) 1999-07-20 2001-02-07 MEDIS S.r.l. Medical Infusion Systems Use of plant polyphenols with vitamines for treating iron overload
WO2001015553A1 (en) 1999-08-27 2001-03-08 Michigan State University Dietary food supplement containing natural cyclooxygenase inhibitors
WO2003080062A1 (en) * 2002-03-25 2003-10-02 Silvia Perrella Segre Composition comprising vitamin b9, vitamin b6, lipoic acid and plant extracts for treating circulatory disorders
EP1683805A1 (en) 2003-10-24 2006-07-26 Meiji Seika Kaisha Ltd. Novel inhibitor for advanced glycation endproduct formation and aldose reductase inhibitor
WO2007038421A2 (en) 2005-09-27 2007-04-05 University Of Kentucky Research Foundation Berry preparations and extracts
EP1882473A1 (en) 2006-07-28 2008-01-30 Indena S.P.A. Use of anthocyanosides to prepare formulations for the treatment of mucositis induced by antitumoral drugs
WO2008016593A2 (en) 2006-07-31 2008-02-07 Trustees Of Columbia University In The City Of New York Bioactive depside and anthocyanin compounds, compositions, and methods of use
JP2008239612A (ja) * 2007-02-28 2008-10-09 Kikkoman Corp 血流改善組成物
WO2008126980A1 (en) 2007-04-11 2008-10-23 Industry-Academic Cooperation Foundation Gyeongsang National University Pharmaceutical composition for wound healing containing anthocyanin extracted from the black soybean seed coat
WO2009059218A1 (en) 2007-10-31 2009-05-07 Phytomedics, Inc. Berry preparations for treatment of diabetes and metabolic syndrome
WO2010131049A2 (en) 2009-05-15 2010-11-18 University Of Leeds Natural hair dyes

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6277328A (ja) * 1985-09-30 1987-04-09 Shiseido Co Ltd 循環改善剤
JP2000212092A (ja) * 1999-01-27 2000-08-02 Yanai Yoshiaki 抗ウイルス・抗菌剤
CN100584841C (zh) * 2007-08-08 2010-01-27 暨南大学 穿心莲内酯衍生物及其在制药中的应用

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997041137A1 (en) 1996-04-17 1997-11-06 Unifob Use of anthocyanidin and anthocyanidin derivatives
EP1074254A2 (en) 1999-07-20 2001-02-07 MEDIS S.r.l. Medical Infusion Systems Use of plant polyphenols with vitamines for treating iron overload
WO2001015553A1 (en) 1999-08-27 2001-03-08 Michigan State University Dietary food supplement containing natural cyclooxygenase inhibitors
WO2003080062A1 (en) * 2002-03-25 2003-10-02 Silvia Perrella Segre Composition comprising vitamin b9, vitamin b6, lipoic acid and plant extracts for treating circulatory disorders
EP1683805A1 (en) 2003-10-24 2006-07-26 Meiji Seika Kaisha Ltd. Novel inhibitor for advanced glycation endproduct formation and aldose reductase inhibitor
WO2007038421A2 (en) 2005-09-27 2007-04-05 University Of Kentucky Research Foundation Berry preparations and extracts
EP1882473A1 (en) 2006-07-28 2008-01-30 Indena S.P.A. Use of anthocyanosides to prepare formulations for the treatment of mucositis induced by antitumoral drugs
WO2008016593A2 (en) 2006-07-31 2008-02-07 Trustees Of Columbia University In The City Of New York Bioactive depside and anthocyanin compounds, compositions, and methods of use
JP2008239612A (ja) * 2007-02-28 2008-10-09 Kikkoman Corp 血流改善組成物
WO2008126980A1 (en) 2007-04-11 2008-10-23 Industry-Academic Cooperation Foundation Gyeongsang National University Pharmaceutical composition for wound healing containing anthocyanin extracted from the black soybean seed coat
WO2009059218A1 (en) 2007-10-31 2009-05-07 Phytomedics, Inc. Berry preparations for treatment of diabetes and metabolic syndrome
US20090176718A1 (en) 2007-10-31 2009-07-09 David Ribnicky Berry Preparations For Treatment Of Diabetes And Metabolic Syndrome
WO2010131049A2 (en) 2009-05-15 2010-11-18 University Of Leeds Natural hair dyes

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
Burns et al., "Phytochemical composition and metabolic performance-enhancing activity of dietary berries traditionally used by Native North Americans," Journal of Agricultural and Food Chemistry, 56:654-660 (2008).
Christian et al., "Antioxidant and cyclooxygenase inhibitory activity of sorrel (Hibiscus sabdariffa)," Journal of Food Composition and Analysis, Academic Press, 19:778-783 (2006).
Diouf et al., "Study on chemical composition, antioxidant and anti-inflammatory activities of hot water extract from Piceamariana bark and its proanthocyanidin-rich fractions," Food Chemistry, 113:897-902 (2009).
Escribano-Bailon et al., "Anthocyanins in berries of Maqui," Phytochemical Analysis: PCA 2006 Pubmed, 17:8-14 (2006).
Grace et al., "Hypoglycemic activity of a novel anthocyanin-rich formulation from lowbush blueberry, Vaccinium angustifolium Aiton," Phytomedicine, Gustav Fischer Verlag, Stuttgart, DE 16:406-415 (2009).
Hwang Mun Kyung et al., "Fyn kinase is a direct molecular target of delphinidin for the inhibition of cyclooxygenase-2 expression induced by tumor necrosis factor-alpha," Biochemical Pharmacology, 77:1213-1222 (2009).
Konstantin et al., "Anthocyanins from black soybean seed coats inhibit UVB-induced inflammatory cyclooxygenase-2 gene expression and PGE2 production through regulation of the nuclear factor-kappaβ and phosphatidylinositol 3-kinase/Akt pathway," Journal of Agricultural and Food Chemistry, 56:8969-8974 (2008).
Kwon et al., "Delphinidin suppresses ultraviolet β-induced cyclooxygenases-2 expression through inhibition of MAPKK4 and PI-3 kinase," Carcinogenesis, 30:1932-1940 (2009).
Nizamutdinova et al., "Anthocyanins from black soybean seed coats stimulate wound healing in fibroblasts and keratinocytes and prevent inflammation in endothelial cells," Food and Chemical Toxicology, Pergamon, GB 47:2806-2812 (2009).
Schreckinger et al., "Antioxidant Capacity and in Vitro Inhibition of Adipogenesis and Inflammation of Phenolic Extracts of Vaccinium floribundum and Aristotelia chilensis," Journal of Agricultural and Food Chemistry, 58:8966-8976 (2010).
Segura-Carretero et al., "Selective extraction, separation, and identification of anthocyanins from Hibiscus sabdariffa L. using solid phase extraction-capillary electrophoresis-mass spectrometry (time-of-flight / ion trap)," Electrophoresis, 29:2852-2861 (2008).
Thomas et al., "Pharmacokinetics of anthocyanidin-3-glycosides following consumption of Hibiscus sabdariffa L. extract," Journal of Clinical Pharmacology, 45:203-210 (2005).

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023150072A1 (en) 2022-02-01 2023-08-10 Sinclair David A Compositions and methods for the preservation of plant matter

Also Published As

Publication number Publication date
ES2618952T3 (es) 2017-06-22
JP6141929B2 (ja) 2017-06-07
US20190151342A1 (en) 2019-05-23
EP2344154B1 (en) 2016-12-07
US20110268825A1 (en) 2011-11-03
KR20120090089A (ko) 2012-08-16
EP2344154A1 (en) 2011-07-20
WO2011048479A3 (en) 2011-08-11
JP2015232038A (ja) 2015-12-24
US20150164932A1 (en) 2015-06-18
KR101625882B1 (ko) 2016-05-31
JP2013508347A (ja) 2013-03-07
CA2735343A1 (en) 2011-04-21
WO2011048479A2 (en) 2011-04-28

Similar Documents

Publication Publication Date Title
US20190151342A1 (en) Compositions that include anthocyanidins and methods of use
Li et al. A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum
JP6415394B2 (ja) 安定化されたアントシアニン組成物
KR102070479B1 (ko) 드라이 아이 예방·치료제
US20090176718A1 (en) Berry Preparations For Treatment Of Diabetes And Metabolic Syndrome
JP5425758B2 (ja) グアバ抽出物
US8679550B2 (en) Morinda citrifolia juice formulations comprising iridoids
US20150086655A1 (en) Morinda Citrifolia Juice Formulations Comprising Iridoids
CN102781435A (zh) 类胡萝卜素与表叶黄素的组合
AU2020326738A1 (en) Oral formulations of cannabis extracts and methods of making same
JPWO2017135466A1 (ja) キサントフィルとヒシ属植物の加工物を含有する組成物
JP5071618B2 (ja) 外分泌腺の機能障害改善剤及び機能障害改善用飲食物
WO2016130942A1 (en) Compositions providing extended energy and methods of use
KR20080088925A (ko) 시력 보호용 조성물
US20080268039A1 (en) Loquat compositions
JP6026719B2 (ja) 視機能予防・改善剤
JP5893438B2 (ja) 網膜症の予防又は改善剤
US20230241149A1 (en) Transthyretin tetramer stabilizing agent, and preventing agent or progression suppressing agent for transthyretin amyloidosis
EP4226920A1 (en) Transthyretin tetramer stabilizer and agent for preventing or suppressing progression of transthyretin amyloidosis
Fruit AmericanHerbal Pharmacopoeia

Legal Events

Date Code Title Description
AS Assignment

Owner name: CONSORCIO DE TECNOLOGIA E INNOVACION PARA LA SALUD S.A., CHILE

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BURGOS, RAFAEL;HANCKE, JUAN;JARA, EVELYN;AND OTHERS;REEL/FRAME:026345/0320

Effective date: 20091127

Owner name: MAQUI NEW LIFE SA (MNL), CHILE

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CONSORCIO DE TECNOLOGIA E INNOVACION PARA LA SALUD S.A.;REEL/FRAME:026345/0529

Effective date: 20110114

Owner name: CONSORCIO DE TECNOLOGIA E INNOVACION PARA LA SALUD

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BURGOS, RAFAEL;HANCKE, JUAN;JARA, EVELYN;AND OTHERS;REEL/FRAME:026345/0320

Effective date: 20091127

STCV Information on status: appeal procedure

Free format text: COURT PROCEEDINGS TERMINATED

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: NOTICE OF ALLOWANCE MAILED -- APPLICATION RECEIVED IN OFFICE OF PUBLICATIONS

STPP Information on status: patent application and granting procedure in general

Free format text: PUBLICATIONS -- ISSUE FEE PAYMENT VERIFIED

STCF Information on status: patent grant

Free format text: PATENTED CASE

AS Assignment

Owner name: PHARMACEUTICAL PATENT ATTORNEYS, LLC, FLORIDA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MAQUI NEW LIFE S.A.;REEL/FRAME:053840/0187

Effective date: 20200921

AS Assignment

Owner name: PHARMACEUTICAL PATENT ATTORNEYS, LLC, NEW JERSEY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MAQUI NEW LIFE S.A.;REEL/FRAME:055633/0125

Effective date: 20200830

FEPP Fee payment procedure

Free format text: MAINTENANCE FEE REMINDER MAILED (ORIGINAL EVENT CODE: REM.); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY